Thrombotic events sometimes complicate erythropoietin therapy. Fibrinolytic system may play a role in their pathogenesis. The studies were performed on 22 chronically hemodialyzed patients with end-stage renal failure treated with recombinant human erythropoietin (rHuEPO, Eprex, Cilag) for 12 weeks. Alpha 2 antiplasmin (alpha 2AP), antithrombin III (AT III), C1 esterase inhibitor (C1 INH), plasminogen activator inhibitor (PAI) activities, alpha 2macroglobulin (alpha 2M), fibrinogen, fibrin monomers concentration and euglobulin clot lysis time (ECLT) were measured before and after 1, 2, 4, 8 and 12 weeks of rHEPO therapy. A fall in PAI activity (p < 0.05) was found after 1 week, while alpha 2AP and C1 INH activities decreased after 12 weeks of the therapy (p < 0.001 and p < 0.05, respectively). The activity of AT III, the main inhibitor of the coagulation cascade fell after 4 weeks of the treatment with rHuEPO (p < 0.001). Fibrin monomers concentration was found to be decreased after 12 weeks of rHuEPO administration. Fibrinogen and alpha 2M concentration showed no statistically significant changes during rHuEPO therapy. A decrease in plasma fibrinolytic inhibitor activities may be considered as a protective mechanism against thrombotic tendency observed during rHuEPO therapy.